Use of Prucalopride in Severe Ileus in a Critically Ill Patient With Acute Alcoholic Hepatitis and Hepatic Encephalopathy

ABSTRACT

Ileus is a common gastrointestinal complication in critically ill patients, posing a unique management challenge due to its multifactorial etiology and impact on clinical stability. Standard therapeutic approaches often fail in the setting of metabolic derangement and hemodynamic instability. Prucalopride, a selective 5-HT₄ receptor agonist, has demonstrated efficacy in promoting colonic motility; however, its use in severe small bowel and colonic ileus or decompensated liver disease populations remains limited. We report the case of a 28-year-old man with decompensated alcoholic hepatitis who developed severe small bowel and colonic ileus refractory to standard management. Concerns for worsening illness prompted a trial of prucalopride, which was temporally associated with rapid resolution of the ileus and remarkable improvement in radiographic imaging and clinical phenotype. Prucalopride may be a potential therapeutic option for severe small bowel and colonic ileus in critically ill patients. Further studies are warranted to delineate its safety and efficacy.

INTRODUCTION

Ileus is a common complication in critically ill patients and is associated with significant morbidity.^1,2 The etiology of ileus in critical illness is often multifactorial, with the usual causes being shock, metabolic derangements, infections, electrolyte imbalance, or medication effects.¹ Conventional management includes bowel rest, nasogastric (NG) decompression, correction of precipitating factors, and cautious use of prokinetic agents, such as metoclopramide, erythromycin, or neostigmine.^1,3,4 However, treatment options remain limited when ileus is refractory to standard care.

Prucalopride is a highly selective and potent serotonin (5-HT₄) receptor agonist that is approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation.^5–7 It enhances coordinated peristaltic contractions primarily in the colon by stimulating enteric neurons.⁴ In 2021, Jandee et al conducted a pilot randomized double-blind placebo-controlled trial evaluating the efficacy of prucalopride in critically ill patients with paralytic ileus.⁸ Prucalopride demonstrated potential benefit in critically ill patients with nonsevere paralytic ileus. The evidence for its efficacy and safety in severe or diffuse small bowel and colonic ileus remains limited.

This report describes the use of prucalopride in effort to resolve diffuse, severe small bowel and colonic ileus refractory to multiple conventional therapies in a critically ill patient with acute decompensated alcoholic cirrhosis.

CASE REPORT

A 28-year-old man with a medical history of severe alcohol use disorder presented to a local hospital with jaundice and encephalopathy. He was initially found to have massive upper gastrointestinal (GI) hemorrhage requiring intubation for airway protection, massive transfusion, and vasopressor support. He was diagnosed with acute alcoholic hepatitis complicated by portal hypertension, esophageal varices, coagulopathy, massive upper GI hemorrhage, hepatic encephalopathy, and acute renal failure requiring continuous renal replacement therapy. He was initially stabilized then transferred to a liver transplant center.

Significant laboratory results show a total bilirubin of 28.9 mg/dL, creatinine of 3.71 mg/dL, sodium of 131 mmol/L, and an international normalized ratio of 2.9. Liver enzymes were markedly elevated with an aspartate aminotransferase of 811 U/L and alanine aminotransferase of 694 U/L, while his ammonia was 82 mcmol/L. His lactate level was within normal limits at 1.3 mmol/L. His Model for End-Stage Liver Disease score was greater than 40. He remained intubated on mechanical ventilation and remained on norepinephrine at 0.07 mcg/kg/min and vasopressin at 0.04 units per minute at the time of transfer.

He had endoscopic control of the upper GI hemorrhage. He was extubated shortly afterward and initially tolerated enteric nutrition. However, on hospital day 4, he developed progressive abdominal distention and minimal stool passage with concern for ileus. NG suctioning revealed large volume bilious output. Abdominal radiographs and computed tomography of the abdomen and pelvis were suggestive of diffuse ileus involving both small bowel and colon with no obvious transition point, mechanical obstruction, or pneumoperitoneum.

The patient's ileus persisted throughout days 5–9 despite bowel rest, NG tube decompression, lactulose and milk-and-molasses enemas, electrolyte optimization, increased physical activity, minimization of narcotics and sedative medications, rectal tube placement, and prokinetic medications including metoclopramide, senna, and neostigmine. Following repeated neostigmine administration, the patient developed significant bronchorrhea and respiratory distress requiring increased oxygen requirements, inhaled bronchodilators, and antimuscarinic agents. In addition, metoclopramide administration was complicated by the development of akathisia. Neostigmine and metoclopramide were discontinued on hospital day 7.

On day 9, despite aggressive treatment outlined above, progressive abdominal distention, firmness, pain, encephalopathy, and rising serum lactate levels to 2.3 mmol/L, prompted concern for impending bowel perforation and possible airway compromise. Low output was noted from NG tube despite continued decompression. Imaging confirmed the severity of the ileus, with the small bowel dilated up to 4.8 cm and the transverse colon dilated to 8.9 cm (Figure 1). The leading differential diagnosis at this time remained diffuse ileus. Obstruction was considered less likely with bowel gas extending to the rectum. The patient's clinical course was considered inconsistent with Ogilvie syndrome given small bowel involvement and absence of response to standard management and neostigmine.⁹

Figure 1.

Abdominal radiograph demonstrating multiple gas-filled loops of small bowel measuring up to 4.8 cm in diameter and colon measuring up to 8.9 cm in diameter, favoring diffuse ileus.

On hospital day 10, given the refractory and clinically worsening ileus, the patient was treated with prucalopride 2 mg through the nasoduodenal tube based on previously published data.^8,10,11 Within 3 hours, he produced 1 L of liquid stool output and had an additional 5.8 L of liquid stool output over the next 24 hours. He continued to demonstrate steady stool output the following days without additional bowel regimen. Repeat abdominal radiographs showed marked improvement in diffuse bowel distention and resolution of ileus within 24 hours of prucalopride administration (Figure 2).

Figure 2.

Follow-up abdominal radiograph demonstrating significant improvement in gaseous distention, no free intraperitoneal air.

The patient did not experience common side effects of worsening nausea, abdominal pain, or headache. His corrected QT was monitored continuously and ranged from 418 to 509 ms in the 24 hours after prucalopride administration, compared with 444–464 ms in the previous 24 hours. No arrhythmias were noted.

The patient demonstrated rapid multiorgan system improvement after ileus resolution and was able to participate fully in multidisciplinary liver transplant evaluation and planning.

DISCUSSION

Prucalopride is a highly potent and selective 5-HT₄ receptor agonist that enhances acetylcholine release from myenteric neurons, stimulating propulsive motility and coordinated peristalsis.^5,6 Compared with older 5-HT₄ agonists, prucalopride demonstrates minimal off-target cardiac effects due to its high receptor selectivity.⁶ Prucalopride is most commonly used as therapy for chronic idiopathic constipation not sufficiently treated with laxatives.⁹

The pilot randomized controlled trial by Jandee et al evaluated prucalopride 2 mg daily in critically ill patients with paralytic ileus and found a shorter time to enteral tolerance and improved bowel movement frequency compared with placebo.⁸ Although other clinical trials and meta-analyses have investigated prucalopride for ileus and other motility disorders, its use in severe ileus, small bowel ileus, and liver disease has limited prior evidence.^7,8,10,11

In this case, prucalopride was temporally associated with rapid resolution of severe small bowel and colonic ileus that was refractory to standard interventions in a critically ill patient with decompensated liver disease. The patient began to demonstrate resolution of ileus approximately 3 hours after administration of 2 mg of prucalopride. This dose was selected based on previous published data using 2 mg daily in critically ill patients. We elected to give a single dose of 2 mg despite the patient's severe renal impairment and continued renal replacement therapy as trial of therapy and to minimize the risk of supratherapeutic levels with repeat dosing. Given repeated, aggressive treatment with prokinetics, cholinergic agonists, electrolyte optimization, and NG decompression over many days with clinical worsening, this argues against coincidental resolution of the ileus after prucalopride administration.

This case expands on the existing literature by demonstrating the potential benefits of prucalopride beyond colonic dysmotility. Given its favorable safety profile, prucalopride may represent a viable therapeutic option for refractory ileus. Further studies are warranted to delineate its safety and efficacy.

DISCLOSURES

Author contributions: A. Swanson wrote the main manuscript text, assisted with the editing process, and prepared Figures 1 and 2. J. Liu assisted with writing the manuscript and throughout the editing process. AN Bektas and JS Schwarz assisted with formatting and editing. All the authors have reviewed and contributed to the knowledge base of this manuscript. A. Swanson is the article guarantor.

Financial disclosure: None to report.

Previous presentation: Mayo Clinic Gastroenterology and Hepatology 2026 Conference, March 11–14, 2026; Amelia Island, FL.

Informed consent was obtained for this case report.